title: FGFR3 transmembrane domain interactions persist in the presence of its extracellular domain.
abstract: Isolated receptor tyrosine kinase transmembrane (TM) domains have been shown to form sequence-specific dimers in membranes. Yet, it is not clear whether studies of isolated TM domains yield knowledge that is relevant to full-length receptors or whether the large glycosylated extracellular domains alter the interactions between the TM helices. Here, we address this question by quantifying the effect of the pathogenic A391E TM domain mutation on the stability of the fibroblast growth factor receptor 3 dimer in the presence of the extracellular domain and comparing these results to the case of the isolated TM fibroblast growth factor receptor 3 domains. We perform the measurements in plasma membrane-derived vesicles using a Förster-resonance-energy-transfer-based method. The effect of the mutation on dimer stability in both cases is the same (∼-1.5 kcal/mol), suggesting that the interactions observed in simple TM-peptide model systems are relevant in a biological context.
authors.affiliation: Department of Materials Sciences and Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Sarvenaz
authors.initials: S
authors.lastname: Sarabipour
authors.forename: Kalina
authors.initials: K
authors.lastname: Hristova
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D055503:Protein Multimerization; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D008051:Lipid Bilayers; D051498:Receptor, Fibroblast Growth Factor, Type 3